Translation efficiency in humans: tissue specificity, global optimization and differences between developmental stages.
Translation efficiency in humans: tissue specificity, global optimization and differences between developmental stages.
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DOI：
10.1093/nar/gkq009
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发表时间：
2010-05
影响因子：
14.9
通讯作者：
Ruppin E
中科院分区：
文献类型：
--
作者：
Waldman YY;Tuller T;Shlomi T;Sharan R;Ruppin E
在单细胞和多细胞生物中的各种研究表明，密码子偏好性通过与tRNA库的共适应在翻译效率（TE）中起着重要作用。然而，在人类和其他哺乳动物中，密码子偏好的作用仍然是一个悬而未决的问题，不同的研究结果相互矛盾。在这里，我们解决这个问题，进行大规模的组织特异性分析TE在人类中，使用tRNA适应指数（tAI）作为TE的直接措施。我们发现tAI与组织特异性和全局表达测量中的表达水平显著相关，证明了人体组织的TE。有趣的是，我们发现成人组织中的相关性显著高于胎儿组织，这表明tRNA库更适合成人时期。基于优化的分析表明，tRNA池密码子偏好共适应是全局（而不是组织特异性）驱动的。此外，我们发现tAI与蛋白质功能重要性相关的几个指标相关，包括基因重要性。使用推断的组织特异性tRNA池导致类似的结果，并表明组织特异性基因比其他基因更适应其tRNA池，并且相关的功能基因组组在每个组织中有效地翻译。在其他哺乳动物中也得到了类似的结果。综上所述，这些结果证明了密码子偏好在人类TE中的作用，并为未来在多细胞生物中研究组织特异性TE铺平了道路。
Various studies in unicellular and multicellular organisms have shown that codon bias plays a significant role in translation efficiency (TE) by co-adaptation to the tRNA pool. Yet, in humans and other mammals the role of codon bias is still an open question, with contradictory results from different studies. Here we address this question, performing a large-scale tissue-specific analysis of TE in humans, using the tRNA Adaptation Index (tAI) as a direct measure for TE. We find tAI to significantly correlate with expression levels both in tissue-specific and in global expression measures, testifying to the TE of human tissues. Interestingly, we find significantly higher correlations in adult tissues as opposed to fetal tissues, suggesting that the tRNA pool is more adjusted to the adult period. Optimization based analysis suggests that the tRNA pool—codon bias co-adaptation is globally (and not tissue-specific) driven. Additionally, we find that tAI correlates with several measures related to the protein functionally importance, including gene essentiality. Using inferred tissue-specific tRNA pools lead to similar results and shows that tissue-specific genes are more adapted to their tRNA pool than other genes and that related sets of functional gene groups are translated efficiently in each tissue. Similar results are obtained for other mammals. Taken together, these results demonstrate the role of codon bias in TE in humans, and pave the way for future studies of tissue-specific TE in multicellular organisms.
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DOI：
10.1073/pnas.96.8.4482
发表时间：
1999-04-13
影响因子：
11.1
作者：
Duret, L;Mouchiroud, D
通讯作者：
Mouchiroud, D
影响因子：
7
作者：
Costantini, M;Clay, O;Bernardi, G
通讯作者：
Bernardi, G
影响因子：
10.7
作者：
EyreWalker, A
通讯作者：
EyreWalker, A
影响因子：
4
作者：
Duret, L
通讯作者：
Duret, L
影响因子：
3.3
作者：
Comeron, JM
通讯作者：
Comeron, JM